The structure and recombinant production of protease nexin-I are described in European patent application 251505, published Jan. 7, 1988, and incorporated herein by reference. The contents of this publication are substantially the same as those of above-referenced Ser. No. 07/025,450, which case is allowed and involved in an interference. As disclosed in these documents, protease nexin-I occurs naturally in two closely related forms, PN-I.alpha. and PN-I.beta., which result from alternate splicing events in the mRNA message encoding the protein. PN-I.alpha. and PN-I.beta. consist of 378 and 379 amino acids, respectively, and differ only in that the arginyl residue at position 310 of PN-I.alpha. is replaced by a thr-gly sequence in PN-I.beta.. PN-I.alpha. and PN-I.beta. can be prepared individually using recombinant means or the natively produced protein can be isolated from various tissue sources such as human fibroblasts or glial cells. Methods for purifying protease nexin-I to apparent homogeneity from fibroblasts have been described by Scott, R. W., et al., J. Biol Chem (1985) 260:7029-7034.
The ability of protease nexin-I to inhibit various anticlotting factors such as urokinase and tissue plasminogen activator is well established. It is also known that protease nexin-I stimulates the growth of neurites. It has now been demonstrated that protease nexin-I is effective in preventing degradation of connective tissue and in the treatment of inflammatory diseases such as arthritis.